Systems that deliver certain drugs to a patient (e.g., targeted to a particular tissue or cell type or targeted to a specific diseased tissue but not normal tissue) or that control release of drugs have long been recognized as beneficial.
For example, therapeutics that include an active drug and that are targeted to a particular tissue or cell type, or targeted to a specific diseased tissue but not to normal tissue, may reduce the amount of the drug in tissues of the body that are not targeted. This is particularly important when treating a condition such as cancer where it is desirable that a cytotoxic dose of the drug is delivered to cancer cells without killing the surrounding non-cancerous tissue. Effective drug targeting may reduce the undesirable and sometimes life threatening side effects common in anticancer therapy. In addition, such therapeutics may allow drugs to reach certain tissues they would otherwise be unable to reach. Therapeutics that offer controlled release and/or targeted therapy also must be able to deliver an effective amount of drug, which is a known limitation in other nanoparticle delivery systems.
For example, a major limitation to traditional cancer treatments is lack of selectivity for cancer cells over healthy cells. Recently, a significant amount of research has been devoted to using nanomedicine to efficiently deliver anticancer agents to tumors. Solid tumors depend on substantial nutrients and oxygen, resulting in exaggerated angiogenesis, which in turn leads to the formation of large gaps between endothelial cells. The leaky vasculature that results leads to size-dependent, e.g. 200-800 nm accumulation of macromolecules and nanoparticles in the tumor. While this form of passive targeting offers an advantage to nanomedicine over free drug, it does not ensure delivery of cargo directly to or into the tumor cell.
Epidermal growth factor receptor (EGFR) is a well understood target that is upregulated in various cancers, has been associated with tumor proliferation, and is generally regarded as a promising receptor for nanotherapeutic targeting. Accordingly, a need exists for targeted nanoparticle therapeutics such as nanoparticles that are capable of targeting EGFR.